Since 1981 a number of aldose reductase inhibitors (ARIs) have been extensively investigated in clinical trials for the treatment or prevention of diabetic complications. In general, the results from these trials have varied from no effect to improvement. In part, the inconclusive results are due to differences in the study designs. Investigation of some ARIs has been discontinued because of lack of efficacy (ponalrestat) or major toxicity (sorbinil). Of the ARIs that have been evaluated, only tolrestat is currently undergoing clinical investigation. Although the most recent studies have shown promising results, the role of ARIs in the treatment or prevention of secondary complications of diabetic neuropathy will be determined in ongoing or future clinical trials.